Evidence map›Paper›PMID 38602454›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association.

Laura Romero-Castillo, Taotao Li, Nhu-Nguyen Do, Outi Sareila, Bingze Xu, Viktoria Hennings, Zhongwei Xu, Carolin Svensson, Ana Oliveira-Coelho, Zeynep Sener and 4 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Article
  7. Genetic association betweenFrontiers in genetics · 2025
    Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Laura Romero-CastilloMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.ORCID 0000-0002-0271-212X
Taotao LiMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Nhu-Nguyen DoMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Outi SareilaMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Bingze XuMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Viktoria HenningsDepartment of Pediatrics, Institute of Clinical Sciences and Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.
Zhongwei XuMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Carolin SvenssonMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Ana Oliveira-CoelhoMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Zeynep SenerMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Vilma UrbonaviciuteMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.
Olov EkwallDepartment of Pediatrics, Institute of Clinical Sciences and Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.
Harald BurkhardtFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
Rikard HolmdahlMedical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden.ORCID 0000-0002-4969-2576

Funding

Academy of FinlandALF-agreement ALFGBG-965795Cancerfonden 222350Pj01HKnut och Alice Wallenbergs Stiftelse 2019-0059Leo Foundation LF-OC-22-001023Spanish Ministry of Universities and NextGeneration EUSwedish Association against RheumatismSwedish Medical Research Council 2019-01209Swedish Medical Research Council 2022-00781Swedish State under the agreement between the Swedish government and the county councils
6 · The paper itself

Abstract

Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non-physiologic expression. To address this, physiologically relevant mouse models are established via knock-in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock-in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen-induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell-mediated arthritis development. In conclusion, the humanized knock-in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII-associated diseases.

Indexed as

AllelesAntigens, Differentiation, B-LymphocyteArthritis, RheumatoidDisease Models, AnimalGene Knock-In TechniquesHistocompatibility Antigens Class IIMice, Inbred C57BLMice, TransgenicAnimalsArthritis, ExperimentalCollagen Type IIHLA-DRB1 ChainsHumansMiceAntigens, Differentiation, B-LymphocyteCollagen Type IIHistocompatibility Antigens Class IIHLA-DRB1 Chainsinvariant chainautoimmune diseasesCIADTHhumanized miceMHC class IIrheumatoid arthritis

Identifiers

PMID38602454
PMCPMC11187888

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.